Organic synthesis provides access to novel chemical entities essential for human health research as biological probes, libraries for high-throughput screening, and even as drug candidates. However, traditional chemical methodology development and reaction optimization leading to compound production are time-consuming processes. Optimizing reactions to ensure that they are reliable enough to work over a range of desired building blocks may take weeks or months using the batch synthesis methods that have been the mainstay of organic synthesis for over a hundred years. Flow synthesis methods, on the other hand, allow small quantities of material to be continuously injected and reacted together. Parameters such as reaction time, temperature and stoichiometry are easy to change and monitor in real time. Whole series of chemical reactions may be set up, run, and analyzed, in short periods of time relative to the amount of time required for batch methods. Because chemical intermediates can be generated in situ using flow technology in small quantities and immediately used, it becomes possible to work with highly reactive or dangerous species that would be difficult to handle in a batch format, opening up new avenues for synthetic innovation. In addition, once reactions are developed using flow, it is typically possible to obtain large quantities of product by carrying out reactions for longer periods of time rather than through traditional scaling up, which often requires laborious re-optimization of conditions to suit different reaction scales. We propose to create a centralized flow synthesis system capable of facilitating research in the development of new chemical methodologies. Major users would be NIH-funded researchers primarily in the departments of Chemistry and Medicinal Chemistry at the University of Kansas, with an additional colleague at the University of Missouri, Kansas City. The major use group would include two major NIH-funded research centers. Support is requested for the purchase of a flow synthesis system integrated with one combined reverse phase high performance liquid chromatography separation system associated with one ultraviolet and one mass spectrophotometric detection system. The intention is to make micro-fluidic and cartridge-based flow synthesis and integrated analysis instrumentation and expertise available to a range of investigators. The instrument will be managed by the staff of the Synthesis Core of the Chemical Methodologies and Library Development Center. The primary features of this plan are: (1) to provide flow synthesis capability to a very active synthesis community, (2) to leverage an existing synthesis core facility and experienced staff to manage and maintain the instrument, (3) to facilitate chemical methodologies for which batch synthesis presents safety concerns and operational deficiencies. HEALTH RELEVANCE: Chemical synthesis provides tools essential for biomedical research, ranging from pharmacological probes necessary for studying complex biological systems to drug candidates, but the availability of such molecules is entirely dependent on having good ways of preparing them. Flow chemistry has become recognized as a viable alternative to traditional batch means of carrying out organic reactions in the fine synthesis laboratory. Specifically, the proposed instrument will enhance speed of reaction development, allow for safe generation and use of highly energetic species, and provide superior access to large quantities of desired materials without the need for expensive and time-consuming "scale up" procedures.